Trifluoroacetic acid → (R)-4-((R)-1-((5-bromo-1-cyclopropyl-1 h-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one
Reaction equation
[Br:1][C:2]1[CH:13]=[C:12]([O:14][C@@H:15]([C@H:17]2[CH2:21][N:20]([C@@H](C3C=CC(OC)=CC=3)C)[C:19](=[O:32])[CH2:18]2)[CH3:16])[C:5]2[N:6]([CH:9]3[CH2:11][CH2:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1.C(O)(C(F)(F)F)=O>>[Br:1][C:2]1[CH:13]=[C:12]([O:14][C@@H:15]([C@H:17]2[CH2:21][NH:20][C:19](=[O:32])[CH2:18]2)[CH3:16])[C:5]2[N:6]([CH:9]3[CH2:10][CH2:11]3)[CH:7]=[N:8][C:4]=2[CH:3]=1Participants
Conditions
- Temperature
- 70 °C
Procedure
(R)-4-((R)-1-((5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 2.74 (2.09 g, 4.19 mmol) was dissolved in TFA (42 mL, 550 mmol). The resulting solution was heated to 70° C. and was stirred for 19 h. The reaction mixture was concentrated and partitioned between EtOAc (100 mL) and saturated aqueous NaHCO3 (75 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (2×75 mL). The combined organic phase was dried over Na—2SO4, filtered, and concentrated, and the crude concentrate was purified by silica gel chromatography (0-20% MeOH in DCM) to provide (R)-4-((R)-1-((5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one (2.75). LCMS-ESI+ (m/z): [M+H]+ calcd for C16H19BrN3O2: 364.07; found: 364.05.
Workup
- concentrationThe reaction mixture was concentrated
- custompartitioned between EtOAc (100 mL) and saturated aqueous NaHCO3 (75 mL)
- customThe phases were separated
- extractionthe aqueous phase was extracted with EtOAc (2×75 mL)
- dry with materialThe combined organic phase was dried over Na—2SO4
- filtrationfiltered
- concentrationconcentrated
- concentrationthe crude concentrate
- customwas purified by silica gel chromatography (0-20% MeOH in DCM)
Sources & evidence
- ORD record
- ord-06b6df9332254e91997d2db15de0cce0
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09376441B2
Reaction notes
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